5-31 KRAFTS Thrombotic Disorders

Question 1

What happens when and embolus breaks off a DVT?

Answer 1

Goes through veins, back to heart, into lungs and causes pulmonary
embolism

Question 2

What are symptoms of DVT (deep venous thrombosus)?

Answer 2

Hot, red leg (b/c blood can get in but not out)

Question 3

What is Virchow’s Triad?

Answer 3

Factors contributing to thrombosis
Endothelial Damage
Stasis
Hypercoagubility

Question 4

What is “stasis?”

Answer 4

Not moving (like sitting on a plane)

Question 5

Why does stasis contribute to thrombosis?

Answer 5

Blood pools and platelets and clotting factors can come together

Question 6

What molecule can carcinoma cells release which increase risk of clotting?

Answer 6

Mucin

Question 7

What factors would make you think a patient might have a Hereditary Thrombotic Disorder?

Answer 7

Young patient
	No obvious cause
	Family history
	Recurrent episodes
	Weird location (anywhere other than leg)

Question 8

What are the 4 things you must know about FACTOR V LEIDEN?

Answer 8

Most common cause of unexplained thromboses
Point mutation in Factor V gene
Factor V can’t be turned off
Dx: genetic testing

Question 9

Why can’t Factor V be turned off in Factor V Leiden?

Answer 9

The genetic mutation prevents its cleavage by Protein C

Question 10

Are PTT and INR helpful in Factor V Leiden Dx?

Answer 10

NO. Patient clots just fine, so those tests won’t show anything.

Question 11

How do you treat Factor V Leiden?

Answer 11

Don’t, unless there’s a Thrombosis
Then: give anticoagulant (usually Coumadin)
If recurrent episodes, consider long term anticoagulant

Question 12

What are the 4 things you must know about ANTITHROMBIN III DEFICIENCY?

Answer 12

ATIII is natural anticoagulant
ATIII potentiated by Heparin
Many gene mutations exist
Very rare

Question 13

What does ATIII inhibit?

Answer 13

Factors IIa (thrombin), VIIa, IXa, Xa, and Xia

Question 14

Can you do genetic testing for ATIII deficiency?

Answer 14

No – too many possible mutations to test

Question 15

How to you test for ATIII deficiency?

Answer 15

Functional testing: take patient’s plasma, put thrombin in it, later see how much thrombin is still active

Question 16

Can homozygotes for ATIII def live?

Answer 16

Nope

Question 17

Tx of ATIII def?

Answer 17

ATIII concentrates required

Question 18

What are the 2 things you must know about PROTEIN C and S DEFICIENCIES?

Answer 18

Warfarin-induced skin necrosis

C deficiency rare; S deficiency super-rare

Question 19

What factors does Protein C inhibit?

Answer 19

Factor Va and VIIIa

Question 20

What is protein S?

Answer 20

Endothelial cell receptor for protein C

Question 21

Dx of Protein C/S def?

Answer 21

Functional testing

Question 22

What’s causing the deficiency of Protein C/S?

Answer 22

Genetic mutation – many different kinds

Question 23

What inhibits Proteins C and S?

Answer 23

Warfarin!

Question 24

How does Warfarin induce skin necrosis in protein C and S deficiencies?

Answer 24

Warfarin -> ↓Protein C and S -> Hypercoagulation -> clots -> necrosis

Question 25

What is purpura fulminans?

Answer 25

Thrombotic state + vascular injury = skin necrosis | Related to Warfarin-induced skin necrosis

Question 26

What is Purpura Fulminans associated with?

Answer 26

Coagulopathies | Sepsis (huge mortality rate)

Question 27

Tx of Purpura Fulminans?

Answer 27

Give protein C

Question 28

What are the 4 things you must know about FACTOR II GENE MUTATION?

Answer 28

Factor II = prothrombin Mutated gene  ↑prothrombin Prothrombin itself is normal Rare in non-Caucasians

Question 29

What are the 4 things you must know about HYPERHOMOCYSTEINEMIA?

Answer 29

Homocysteine converts folate Homocysteinuria = rare metabolic disorder Too much homocysteine = thromboses Homocysteinemia has many causes

Question 30

What is bad about too much homocysteine?

Answer 30

Toxic to endothelium (via ROS) | Interferes w/ NO (vasodilator and antithrombotic)

Question 31

What are the 4 things you must know about ANTIPHOSPHOLIPID ANTIBODIES?

Answer 31

Auto-Ab’s against phospholipids Falsely ↑INR May cause thromboses Antiphospholipid syndrome is serious

Question 32

What kind of Ab’s are antiphospholipid Ab’s?

Answer 32

IgG

Question 33

What do the Antiphospholipid Ab’s do?

Answer 33

Bind to phospholipids | Screw up tests

Question 34

What’s an easier name for Antiphospholipid Ab’s?

Answer 34

Inhibitors (inhibit coagulation in vitro)

Question 35

What is the paradox surrounding these inhibitors?

Answer 35

Inhibit coag in vitro | BUT they promote coag in vivo!

Question 36

How do you detect these Ab’s?

Answer 36

PTT Mixing study! If PTT doesn’t correct, inhibitors are present

Question 37

What is Antiphospholipid Antibody Syndrome?

Answer 37

``` Recurrent thrombosis Recurrent spontaneous abortions Increased stroke risk Pulmonary hypertension (clots in lungs) Renal failure (clots in kidneys) ```

Question 38

Under what conditions might you see these Ab’s develop?

Answer 38

Kids – infection Adults – autoimmune disease Elderly - drugs